tbuckley/cabot-search huggingface dataset:
Anti-CD37 α-amanitin–conjugated antibodies as potential therapeutic weapons for Richter syndrome
Authors: Tiziana Vaisitti, Nicoletta Vitale, Matilde Micillo, Lorenzo Brandimarte, Andrea Iannello, Mauro Giulio Papotti, Ozren Jaksic, Gianluca Lopez, Arianna Di Napoli, Juan Carlos Cutrin, Christian Orlik, Michael Kulke, Andreas Pahl, Silvia Deaglio
Journal: Blood (2022)
Non-vasogenic cystoid maculopathies
Authors: Alain Gaudric, Isabelle Audo, Catherine Vignal, Aude Couturier, Élise Boulanger-Scemama, Ramin Tadayoni, Salomon Yves Cohen
Journal: Progress in Retinal and Eye Research (2022)

Besides cystoid macular edema due to a blood-retinal barrier breakdown, another type of macular cystoid spaces referred to as non-vasogenic cystoid maculopathies (NVCM) may be detected on optical coherence tomography but not on fluorescein angiography. Various causes may disrupt retinal cell cohesion or impair retinal pigment epithelium (RPE) and Müller cell functions in the maintenance of retinal dehydration, resulting in cystoid spaces formation. Tractional causes include vitreomacular traction, epiretinal membranes and myopic foveoschisis. Surgical treatment does not always allow cystoid space resorption. In inherited retinal dystrophies, cystoid spaces may be part of the disease as in X-linked retinoschisis or enhanced S-cone syndrome, or occur occasionally as in bestrophinopathies, retinitis pigmentosa and allied diseases, congenital microphthalmia, choroideremia, gyrate atrophy and Bietti crystalline dystrophy. In macular telangiectasia type 2, cystoid spaces and cavitations do not depend on the fluid leakage from telangiectasia. Various causes affecting RPE function may result in NVCM such as chronic central serous chorioretinopathy and paraneoplastic syndromes. Non-exudative age macular degeneration may also be complicated by intraretinal cystoid spaces in the absence of fluorescein leakage. In these diseases, cystoid spaces occur in a context of retinal cell loss. Various causes of optic atrophy, including open-angle glaucoma, result in microcystoid spaces in the inner nuclear layer due to a retrograde transsynaptic degeneration. Lastly, drug toxicity may also induce cystoid maculopathy. Identifying NVCM on multimodal imaging, including fluorescein angiography if needed, allows guiding the diagnosis of the causative disease and choosing adequate treatment when available.
Cost-effectiveness of second-line axicabtagene ciloleucel in relapsed refractory diffuse large B-cell lymphoma
Authors: Swetha Kambhampati, Monica Saumoy, Yecheskel Schneider, Steve Serrao, Pejman Solaimani, Lihua Elizabeth Budde, Matthew G. Mei, Leslie L. Popplewell, Tanya Siddiqi, Jasmine Zain, Stephen J. Forman, Larry W. Kwak, Steven T. Rosen, Alexey V. Danilov, Alex F. Herrera, Nikhil R. Thiruvengadam
Journal: Blood (2022)
MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Chengyue Wu, Angela M. Jarrett, Zijian Zhou, Nabil Elshafeey, Beatriz E. Adrada, Rosalind P. Candelaria, Rania M.M. Mohamed, Medine Boge, Lei Huo, Jason B. White, Debu Tripathy, Vicente Valero, Jennifer K. Litton, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M. Rauch, Thomas E. Yankeelov
Journal: Cancer Research (2022)

Triple-negative breast cancer (TNBC) is persistently refractory to therapy, and methods to improve targeting and evaluation of responses to therapy in this disease are needed. Here, we integrate quantitative MRI data with biologically based mathematical modeling to accurately predict the response of TNBC to neoadjuvant systemic therapy (NAST) on an individual basis. Specifically, 56 patients with TNBC enrolled in the ARTEMIS trial (NCT02276443) underwent standard-of-care doxorubicin/cyclophosphamide (A/C) and then paclitaxel for NAST, where dynamic contrast-enhanced MRI and diffusion-weighted MRI were acquired before treatment and after two and four cycles of A/C. A biologically based model was established to characterize tumor cell movement, proliferation, and treatment-induced cell death. Two evaluation frameworks were investigated using: (i) images acquired before and after two cycles of A/C for calibration and predicting tumor status after A/C, and (ii) images acquired before, after two cycles, and after four cycles of A/C for calibration and predicting response following NAST. For Framework 1, the concordance correlation coefficients between the predicted and measured patient-specific, post-A/C changes in tumor cellularity and volume were 0.95 and 0.94, respectively. For Framework 2, the biologically based model achieved an area under the receiver operator characteristic curve of 0.89 (sensitivity/specificity = 0.72/0.95) for differentiating pathological complete response (pCR) from non-pCR, which is statistically superior (P &amp;lt; 0.05) to the value of 0.78 (sensitivity/specificity = 0.72/0.79) achieved by tumor volume measured after four cycles of A/C. Overall, this model successfully captured patient-specific, spatiotemporal dynamics of TNBC response to NAST, providing highly accurate predictions of NAST response.
Engineering naturally occurring CD7− T cells for the immunotherapy of hematological malignancies
Authors: Abdullah Freiwan, Jaquelyn T. Zoine, Jeremy Chase Crawford, Abishek Vaidya, Stefan A. Schattgen, Jacquelyn A. Myers, Sagar L. Patil, Mahsa Khanlari, Hiroto Inaba, Jeffery M. Klco, Charles G. Mullighan, Giedre Krenciute, Peter J. Chockley, Swati Naik, Deanna M. Langfitt, Maksim Mamonkin, Esther A. Obeng, Paul G. Thomas, Stephen Gottschalk, M. Paulina Velasquez
Journal: Blood (2022)

Chimeric antigen receptor (CAR) T-cell therapy targeting T-cell acute lymphoblastic leukemia (T-ALL) faces limitations such as antigen selection and limited T-cell persistence. CD7 is an attractive antigen for targeting T-ALL, but overlapping expression on healthy T cells leads to fratricide of CD7-CAR T cells, requiring additional genetic modification. We took advantage of naturally occurring CD7- T cells to generate CD7-CAR (CD7-CARCD7-) T cells. CD7-CARCD7- T cells exhibited a predominantly CD4+ memory phenotype and had significant antitumor activity upon chronic antigen exposure in vitro and in xenograft mouse models. Based on these encouraging results, we next explored the utility of CD7- T cells for the immunotherapy of CD19+ hematological malignancies. Direct comparison of nonselected (bulk) CD19-CAR and CD19-CARCD7- T cells revealed that CD19-CARCD7- T cells had enhanced antitumor activity compared with their bulk counterparts in vitro and in vivo. Lastly, to gain insight into the behavior of CD19-CAR T cells with low levels of CD7 gene expression (CD7lo) in humans, we mined single-cell gene and T-cell receptor (TCR) expression data sets from our institutional CD19-CAR T-cell clinical study. CD19-CARCD7lo T cells were present in the initial CD19-CAR T-cell product and could be detected postinfusion. Intriguingly, the only functional CD4+ CD19-CAR T-cell cluster observed postinfusion exhibited CD7lo expression. Additionally, samples from patients responsive to therapy had a higher proportion of CD7lo T cells than nonresponders (NCT03573700). Thus, CARCD7- T cells have favorable biological characteristics and may present a promising T-cell subset for adoptive cell therapy of T-ALL and other hematological malignancies.
Highlights of This Issue
Journal: Clinical Cancer Research (2018)

BRAF-HSP90 Inhibition in MelanomaMultiple mechanisms of BRAF inhibitor therapy escape have been reported, many of which involve proteins that are clients of heat shock protein (HSP)-90.The study by Eroglu and colleagues describes a phase I clinical trial of the BRAF inhibitor vemurafenib in combination with the HSP90 inhibitor XL888 in patients with advanced BRAF-mutant melanoma.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2018)

Panning for Tumor-Specific T Cells on Organoids Cancer immunotherapies have been largely successful; however, some patients fail to respond to these therapies, necessitating the need to predict whether patients will respond to treatment and the likely mechanisms of resistance.Dijkstra and colleagues cocultured tumor organoids from patients with colorectal and lung adenocarcinoma with their own peripheral blood T cells.Coculture enabled selective expansion of tumor-specific T cells, even from precursor populations undetectable in blood.Organoids were treated with IFNg to increase MHCI expression on tumor cells.Addition of anti-PD1 antibodies prevented tumor-mediated inhibition of T-cell proliferation.The CD8 þ T-cell responses were truly tumor specific, as control cocultures with healthy tissue organoids did not exhibit T-cell reactivity.The expanded cytotoxic T cells, when mixed back with tumor organoids, demonstrated T-cell receptor-mediated tumor cell killing in real time.Expert Commentary: Tumor organoids provide a novel platform to generate tumor-specific T cells for investigating tumor-immune interactions in cancer and for personalized immunotherapy.(Image courtesy of
Endoscopy International Open – recently published
Journal: Endoscopy (2018)

Comment on: Linked color imaging improves detection of minimal change esophagitis in non-erosive reflux esophagitis patientsEndosc Int Open 2018; 06(10): E1177-E1183DOI: 10.1055/a-0602-3997 Comment on: EUS fine-needle pancreatic core biopsy can determine eligibility for tumor-agnostic immunotherapyEndosc Int Open 2018; 06(10): E1278-E1282DOI: 10.1055/a-0650-4447 Comment on: Endoscopic full-thickness resection in the colorectum: a single-center case series evaluating indication, efficacy and safetyEndosc Int Open 2018; 06(10): E1227-E1234DOI: 10.1055/a-0672-1138
Evaluating the Performance of Centers for Disease Control and Prevention COVID-19 Community Levels as Leading Indicators of COVID-19 Mortality
Authors: Joshua A. Salomon, Alyssa Bilinski
Journal: Annals of Internal Medicine (2022)

Centers for Disease Control and Prevention (CDC) defines low, medium, and high "COVID-19 community levels" to guide interventions, but associated mortality rates have not been reported. To evaluate the diagnostic performance of CDC COVID-19 community level metrics as predictors of elevated community mortality risk. Time series analysis over the period of 30 May 2021 through 4 June 2022. U.S. states and counties. U.S. population. CDC "COVID-19 community level" metrics based on hospital admissions, bed occupancy, and reported cases; reported COVID-19 deaths; and sensitivity, specificity, and predictive values for CDC and alternative metrics. Mean and median weekly mortality rates per 100 000 population after onset of high COVID-19 community level 3 weeks prior were, respectively, 2.6 and 2.4 (interquartile range [IQR], 1.7 to 3.1) across 90 high episodes in states and 4.3 and 2.1 (IQR, 0 to 5.4) across 7987 high episodes in counties. In 85 of 90 (94%) episodes in states and 4801 of 7987 (60%) episodes in counties, lagged weekly mortality after onset exceeded 0.9 per 100 000 population, and in 57 of 90 (63%) episodes in states and 4018 of 7987 (50%) episodes in counties, lagged weekly mortality after onset exceeded 2.1 per 100 000, which is equivalent to approximately 1000 daily deaths in the national population. Alternative metrics based on lower hospital admissions or case thresholds were associated with lower mortality and had higher sensitivity and negative predictive value for elevated mortality, but the CDC metrics had higher specificity and positive predictive value. Ratios between cases, hospitalizations, and deaths have varied substantially over time. Aggregate mortality does not account for nonfatal outcomes or disparities. Continuing evolution of viral variants, immunity, clinical interventions, and public health mitigation strategies complicate prediction for future waves. Designing metrics for public health decision making involves tradeoffs between identifying early signals for action and avoiding undue restrictions when risks are modest. Explicit frameworks for evaluating surveillance metrics can improve transparency and decision support. Council of State and Territorial Epidemiologists.
Patients surviving COVID-19 had increased risk for incident diabetes vs. persons without COVID-19
Authors: Victor M. Montori
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubAugust 2022Patients surviving COVID-19 had increased risk for incident diabetes vs. persons without COVID-19Victor M. Montori, MD, MScVictor M. Montori, MD, MScMayo Clinic, Rochester, Minnesota, USA (V.M.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0052 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationXie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022;10:311-21. https://pubmed.ncbi.nlm.nih.gov/35325624Clinical Impact RatingsGIM/FP/GP: Hospitalists: Endocrinology: References1. Scherer PE, Kirwan JP, Rosen CJ. Post-acute sequelae of COVID-19: a metabolic perspective. Elife. 2022;11:e78200. [PMID: 35318939] Google Scholar2. Belanger MJ, Hill MA, Angelidi AM, et al. Covid-19 and disparities in nutrition and obesity. N Engl J Med. 2020; 383:e69. [PMID: 32668105] Google Scholar3. Montori V. Why we need to end social COVID and establish care to replenish joy. KevinMD.com. 3 Oct 2021. Accessed at www.kevinmd.com/2021/10/why-we-need-to-end-social-covid-and-establish-care-to-replenish-joy.html on 4 May 2022. Google Scholar4. Spencer Bonilla G, Rodriguez-Gutierrez R, Montori VM. What we don't talk about when we talk about preventing type 2 diabetes—addressing socioeconomic disadvantage. JAMA Intern Med. 2016;176:1053-4. [PMID: 27367180] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mayo Clinic, Rochester, Minnesota, USA (V.M.M.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0052.This article was published at Annals.org on 2 August 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics August 2022Volume 175, Issue 8Page: JC93KeywordsBody mass indexCOVID-19Diabetes medicationsDisclosureHemoglobinHospitalizationsIntensive care unitsInternational Classification of DiseasesLong-term careRacial and ethnic issues ePublished: 2 August 2022 Issue Published: August 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
HAlign 3: Fast Multiple Alignment of Ultra-Large Numbers of Similar DNA/RNA Sequences
Authors: Furong Tang, Jiannan Chao, Yanming Wei, Fenglong Yang, Yixiao Zhai, Lei Xu, Quan Zou
Journal: Molecular Biology and Evolution (2022)

Abstract HAlign is a cross-platform program that performs multiple sequence alignments based on the center star strategy. Here we present two major updates of HAlign 3, which helped improve the time efficiency and the alignment quality, and made HAlign 3 a specialized program to process ultra-large numbers of similar DNA/RNA sequences, such as closely related viral or prokaryotic genomes. HAlign 3 can be easily installed via the Anaconda and Java release package on macOS, Linux, Windows subsystem for Linux, and Windows systems, and the source code is available on GitHub (https://github.com/malabz/HAlign-3).
In drug-refractory IBS, group CBT with interoceptive exposure improved symptoms and QoL at 13 wk
Authors: Daniel Oliver, Nicholas J. Talley
Journal: Annals of Internal Medicine (2022)

Source Citation Kikuchi S, Oe Y, Ito Y, et al. Group cognitive–behavioral therapy with interoceptive exposure for drug-refractory irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2022;117:668-77. 35103022
Deep Learning Electrocardiographic Analysis for Detection of Left-Sided Valvular Heart Disease
Authors: Pierre Elias, Timothy J. Poterucha, Vijay Rajaram, Luca Matos Moller, Victor Rodriguez, Shreyas Bhave, Rebecca T. Hahn, Geoffrey Tison, Sean A. Abreau, Joshua Barrios, Jessica Nicole Torres, J. Weston Hughes, Marco V. Perez, Joshua Finer, Susheel Kodali, Omar Khalique, Nadira Hamid, Allan Schwartz, Shunichi Homma, Deepa Kumaraiah, David J. Cohen, Mathew S. Maurer, Andrew J. Einstein, Tamim Nazif, Martin B. Leon, Adler J. Perotte
Journal: Journal of the American College of Cardiology (2022)

Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR). This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination. A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model. The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively. Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.
Pharmacogenetics of Antiplatelet Therapy
Authors: Matteo Castrichini, Jasmine A. Luzum, Naveen Pereira
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Antiplatelet therapy is used in the treatment of patients with acute coronary syndromes, stroke, and those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used antiplatelet P2Y12 inhibitor in clinical practice. Genetic variation in
Awake Prone Positioning in COVID-19
Authors: Héctor David Meza-Comparán, Jose Victor Jimenez, Orlando Rubén Pérez-Nieto
Journal: JAMA Internal Medicine (2022)

Edward Tang Qian, MD; Cheryl L. Gatto, PhD; Olga Amusina, DNP; Mary Lynn Dear, PhD; William Hiser, BA; Reagan Buie, MHA; Sunil Kripalani, MD; Frank E. Harrell Jr, PhD; Robert E. Freundlich, MD, MS, MSCI; Yue Gao, MS; Wu Gong, MD, MS; Cassandra Hennessy, MS; Jillann Grooms, MSN; Megan Mattingly, MSN; Shashi K. Bellam, MD; Jessica Burke, MD; Arwa Zakaria, DO; Eduard E. Vasilevskis, MD; Frederic T. Billings IV, MD, MSc; Jill M. Pulley, MBA; Gordon R. Bernard, MD; Christopher J. Lindsell, PhD; Todd W. Rice, MD, MSc; Vanderbilt Learning Healthcare System Platform Investigators; Robert Dittus; Shon Dwyer; Paul Harris; Tina Hartert; Jim Hayman; Catherine Ivory; Kevin Johnson; Ruth Kleinpell; Lee Ann Liska; Patrick Luther; Jay Morrison; Thomas Nantais; Mariann Piano; Kris Rhem; Russell Rothman; Matt Semler; Robin Steaban; Philip Walker; Consuelo Wilkins; Adam Wright ; Autumn Zuckerman
Association of Racial Disparities With In-Hospital Outcomes in Severe Bronchopulmonary Dysplasia
Authors: Tamorah R. Lewis, Matthew J. Kielt, Valencia P. Walker, Jonathan C. Levin, Milenka Cuevas Guaman, Howard B. Panitch, Leif D. Nelin, Steven H. Abman, Richard Sindelar, William E Truog, J Michael Collaco, Martin Keszler, Paul E Moore, Bruce Schulman, Beena G Sood, Lystra P Hayden, A Ioana Cristea, Khanh Lai, Lawrence M Rhein, Sherry E Courtney, David N Cornfield, Robert J DiGeronimo, Manvi Bansal, Susan J Gage, Rajeev Bhatia, Roopa Siddaiah, Antonia P Papova, Megan B Lagoski, Joanne M Lagatta
Journal: JAMA Pediatrics (2022)

Bronchopulmonary dysplasia (BPD) is the most common serious morbidity of preterm birth. Short-term respiratory outcomes for infants with the most severe forms of BPD are highly variable. The mechanisms that explain this variability remain unknown and may be mediated by racial disparities.
Awake Prone Positioning in COVID-19: Signal or Noise?
Authors: Ivan Pavlov, Miguel Ibarra-Estrada, Stephan Ehrmann
Journal: JAMA Internal Medicine (2022)

Edward Tang Qian, MD; Cheryl L. Gatto, PhD; Olga Amusina, DNP; Mary Lynn Dear, PhD; William Hiser, BA; Reagan Buie, MHA; Sunil Kripalani, MD; Frank E. Harrell Jr, PhD; Robert E. Freundlich, MD, MS, MSCI; Yue Gao, MS; Wu Gong, MD, MS; Cassandra Hennessy, MS; Jillann Grooms, MSN; Megan Mattingly, MSN; Shashi K. Bellam, MD; Jessica Burke, MD; Arwa Zakaria, DO; Eduard E. Vasilevskis, MD; Frederic T. Billings IV, MD, MSc; Jill M. Pulley, MBA; Gordon R. Bernard, MD; Christopher J. Lindsell, PhD; Todd W. Rice, MD, MSc; Vanderbilt Learning Healthcare System Platform Investigators; Robert Dittus; Shon Dwyer; Paul Harris; Tina Hartert; Jim Hayman; Catherine Ivory; Kevin Johnson; Ruth Kleinpell; Lee Ann Liska; Patrick Luther; Jay Morrison; Thomas Nantais; Mariann Piano; Kris Rhem; Russell Rothman; Matt Semler; Robin Steaban; Philip Walker; Consuelo Wilkins; Adam Wright ; Autumn Zuckerman
Mental health and periodontal and peri‐implant diseases
Authors: Jake Ball, Ivan Darby
Journal: Periodontology 2000 (2022)

Abstract Mental health disorders, particularly depression and anxiety, affect a significant number of the global population. Several pathophysiological pathways for these disorders have been identified, including the hypothalamic‐pituitary‐adrenal axis, autonomic nervous system, and the immune system. In addition, life events, environmental factors, and lifestyle affect the onset, progression, and recurrence of mental health disorders. These may all overlap with periodontal and/or peri‐implant disease. Mental health disorders are associated with more severe periodontal disease and, in some cases, poorer healing outcomes to nonsurgical periodontal therapy. They can result in behavior modification, such as poor oral hygiene practices, tobacco smoking, and alcohol abuse, which are also risk factors for periodontal disease and, therefore, may have a contributory effect. Stress has immunomodulatory effects regulating immune cell numbers and function, as well as proinflammatory cytokine production. Stress markers such as cortisol and catecholamines may modulate periodontal bacterial growth and the expression of virulence factors. Stress and some mental health disorders are accompanied by a low‐grade chronic inflammation that may be involved in their relationship with periodontal disease and vice versa. Although the gut microbiome interacting with the central nervous system (gut‐brain axis) is thought to play a significant role in mental illness, less is understood about the role of the oral microbiome. The evidence for mental health disorders on implant outcomes is lacking, but may mainly be through behaviourial changes. Through lack of compliance withoral hygiene and maintenance visits, peri‐implant health can be affected. Increased smoking and risk of periodontal disease may also affect implant outcomes. Selective serotonin reuptake inhibitors have been linked with higher implant failure. They have an anabolic effect on bone, reducing turnover, which could account for the increased loss.